CD95-mediated alteration in Hsp70 levels is dependent on protein stabilization

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)


Interna författare/redaktörer


Publikationens författare: Concannon CG, FitzGerald U, Holmberg CI, Szegezdi E, Sistonen L, Samali A
Förläggare: ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS
Publiceringsår: 2005
Tidskrift: Cell Stress and Chaperones
Tidskriftsakronym: CELL STRESS CHAPERON
Volym: 10
Nummer: 1
Artikelns första sida, sidnummer: 59
Artikelns sista sida, sidnummer: 65
Antal sidor: 7
ISSN: 1355-8145


Abstrakt

Engagement of death receptors induces caspase activation and apoptosis. A recent study reported altered protein expression, including increased Hsp70 levels during CD95-mediated apoptosis. Here, we examined the mechanism underlying increased Hsp70 levels in cells challenged with a monoclonal antibody directed against the CD95 receptor. Levels of Hsp70 were found to increase in a dose-dependent manner, occurring independently of either heat shock factor 1 activation or the accumulation of Hsp70 messenger ribonucleic acid (mRNA), suggesting the involvement of posttranslational modifications. Inhibition of translation and de novo protein synthesis by cycloheximide resulted in Hsp70 protein levels diminishing over time in control cells, whereas its level remained constant during CD95 signaling. In addition, death receptor activation through exposure of cells to tumor necrosis factor-related apoptosis-inducing ligand did not alter Hsp70 levels. These findings demonstrate that receptor-specific Signaling through the CD95 increases the stability of Hsp70 protein, rather than mRNA, when compared with control cells. The results describe a novel mechanism of heat shock protein accumulation, where increased protein stability and reduced turnover, is the mechanism by which Hsp70 accumulates in cells during CD95-mediated apoptosis.

Senast uppdaterad 2019-17-10 vid 03:05